Albert O. Gee

The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers

Aligned electrospun scaffolds are promising tools for engineering fibrous musculoskeletal tissues, as they reproduce the mechanical anisotropy of these tissues and can direct ordered neo-tissue formation. However, these scaffolds suffer from a slow cellular infiltration rate, likely due in part to their dense fiber packing. We hypothesized that cell ingress could be expedited in scaffolds by increasing porosity, while at the same time preserving overall scaffold anisotropy. To test this hypothesis, poly(epsilon-caprolactone) (a slow-degrading polyester) and poly(ethylene oxide) (a water-soluble polymer) were co-electrospun from two separate spinnerets to form dual-polymer composite fiber-aligned scaffolds. Adjusting fabrication parameters produced aligned scaffolds with a full range of sacrificial (PEO) fiber contents. Tensile properties of scaffolds were functions of the ratio of PCL to PEO in the composite scaffolds, and were altered in a predictable fashion with removal of the PEO component. When seeded with mesenchymal stem cells (MSCs), increases in the starting sacrificial fraction (and porosity) improved cell infiltration and distribution after three weeks in culture. In pure PCL scaffolds, cells lined the scaffold periphery, while scaffolds containing >50% sacrificial PEO content had cells present throughout the scaffold. These findings indicate that cell infiltration can be expedited in dense fibrous assemblies with the removal of sacrificial fibers. This strategy may enhance in vitro and in vivo formation and maturation of functional constructs for fibrous tissue engineering.

The Biomechanical Function of the Anterolateral Ligament of the Knee

Background: Recent anatomic investigations of the lateral structures of the knee have identified a new ligament, called the anterolateral ligament (ALL). To date, the anterolateral ligament has not been biomechanically tested to determine its function. Hypothesis: The ALL of the knee will resist internal rotation at high angles of flexion but will not resist anterior drawer forces. Study Design: Controlled laboratory study. Methods: Eleven cadaveric knees were subjected to 134 N of anterior drawer at flexion angles between 0° and 90° and separately to 5 N·m of internal rotation at the same flexion angles. The in situ forces of the ALL, anterior cruciate ligament (ACL), and lateral collateral ligament (LCL) were determined by the principle of superposition. Results: The contribution of the ALL during internal rotation increased significantly with increasing flexion, whereas that of the ACL decreased significantly. At knee flexion angles greater than 30°, the contribution of the ALL exceeded that of the ACL. During anterior drawer, the forces in the ALL were significantly less than the forces in the ACL at all flexion angles (P < .001). The forces in the LCL were significantly less than those in either the ACL or the ALL at all flexion angles for both anterior drawer and internal rotation (P < .001). Conclusion: The ALL is an important stabilizer of internal rotation at flexion angles greater than 35°; however, it is minimally loaded during anterior drawer at all flexion angles. The ACL is the primary resister during anterior drawer at all flexion angles and during internal rotation at flexion angles less than 35°. Clinical Relevance: Damage to the ALL of the knee could result in knee instability at high angles of flexion. It is possible that a positive pivot-shift sign may be observed in some patients with an intact ACL but with damage to the ALL. This work may have implications for extra-articular reconstruction in patients with chronic anterolateral instability.

Rotator Cuff Repair: Published Evidence on Factors Associated With Repair Integrity and Clinical Outcome

Background: Rotator cuff tears are common, and rotator cuff repair represents a major health care expense. While patients often benefit from rotator cuff repair, anatomic failure of the repair is not unusual. Purpose: To identify the published evidence on the factors associated with retears and with suboptimal clinical outcomes of rotator cuff repairs. Study Design: Systematic review and meta-analysis of articles with evidence levels 1-4. Methods: A total of 2383 articles on rotator cuff repairs published between 1980 and 2012 were identified. Only 108 of these articles, reporting on over 8011 shoulders, met the inclusion criteria of reporting quantitative data on both imaging and clinical outcomes after rotator cuff repair. Factors related to the patients, their shoulders, the procedures, and the results were systematically categorized and submitted for meta-analysis. Results: While the number of relevant articles published per year increased dramatically over the period of the study, the clinical and anatomic results did not show improvement over this period. The weighted mean retear rate was 26.6% at a mean of 23.7 months after surgery. Retears were associated with more fatty infiltration, larger tear size, advanced age, and double-row repairs. Clinical improvement averaged 72% of the maximum possible improvement. Patient-reported outcomes were generally improved whether or not the repair restored the integrity of the rotator cuff. The inconsistent and incomplete data in the published articles limited the meta-analysis of factors affecting the outcome of rotator cuff repair. Conclusion: In spite of a dramatic increase in the number of publications per year, there is little evidence that the results of rotator cuff repair are improving. The information needed to guide the management of this commonly treated and costly condition is seriously deficient. To accumulate the evidence necessary to inform practice, future clinical studies on the outcome of rotator cuff repair must report important data relating to each patient’s condition, the surgical technique, the outcome in terms of integrity, and the change in patient self-assessed comfort and function.

THE INFLUENCE OF AN ALIGNED NANOFIBROUS TOPOGRAPHY ON HUMAN MESENCHYMAL STEM CELL FIBROCHONDROGENESIS

Fibrocartilaginous tissues serve critical load-bearing functions in numerous joints throughout the body. As these structures are often injured, there exists great demand for engineered tissue for repair or replacement. This study assessed the ability of human marrow-derived mesenchymal stem cells (MSCs) to elaborate a mechanically functional, fibrocartilaginous matrix in a nanofibrous microenvironment. Nanofibrous scaffolds, composed of ultra-fine biodegradable polymer fibers, replicate the structural and mechanical anisotropy of native fibrous tissues and serve as a 3D micro-pattern for directing cell orientation and ordered matrix formation. MSCs were isolated from four osteoarthritic (OA) patients, along with meniscal fibrochondrocytes (FC) which have proven to be a potent cell source for engineering fibrocartilage. Cell-seeded nanofibrous scaffolds were cultured in a chemically-defined medium formulation and mechanical, biochemical, and histological features were evaluated over 9 weeks. Surprisingly, and contrary to previous studies with juvenile bovine cells, matrix assembly by adult human MSCs was dramatically hindered compared to donor-matched FCs cultured similarly. Unlike FCs, MSCs did not proliferate, resulting in sparsely colonized constructs. Increases in matrix content, and therefore changes in tensile properties, were modest in MSC-seeded constructs compared to FC counterparts, even when normalized to the lower cell number in these constructs. To rule out the influence of OA sourcing on MSC functional potential, constructs from healthy young donors were generated; these constructs matured no differently than those formed with OA MSCs. Importantly, there was no difference in matrix production of MSCs and FCs when cultured in pellet form, highlighting the sensitivity of human MSCs to their 3D microenvironment.

Compartment syndrome in tibial fractures

Objectives: Compartment syndrome is a devastating complication of tibial fractures. The purpose of this study was to investigate the rate of clinically determined compartment syndrome requiring surgical intervention in tibial fractures by anatomical region and to identify the associated patient and injury factors. Design: Retrospective cohort. Setting: University level I trauma center. Patients/Participants: Acute tibial fractures in 414 patients from January 1, 2004 through October 31, 2006. Methods: Tibial fractures in 414 patients met the inclusion and exclusion criteria. The fractures were classified into 3 groups (proximal, diaphyseal, and distal) based on the anatomic location of the fractures (AO/OTA fractures 41, 42, and 43, respectively). To determine the patient and injury factors associated with the development of compartment syndrome in tibial fractures, the following data were obtained: patient age and sex, mechanism of injury, presence of associated fractures, presence of concomitant head/chest/abdominal/pelvic injury, blood pressure upon admission, open versus closed fracture (Gustilo-Anderson classification if open), status of the fibula, and AO/OTA classification of the tibial fracture. Main Outcome Measures: Rate of clinically determined compartment syndrome requiring fasciotomy by anatomical region of the tibia. Results: The rate of compartment syndrome was highest in the diaphyseal group (8.1%, P < 0.05) followed by proximal (1.6%) and distal (1.4%) groups. The diaphyseal group was further analyzed according to patient and injury factors. Patients who developed compartment syndrome were significantly younger (27.5 years ± 11.7 SD versus 39.0 years ± 16.7 SD, P = 0.003, Student t test) than those who did not develop compartment syndrome. The mean arterial pressures upon admission of the patients who developed compartment syndrome were also found to be slightly higher (107 versus 98.5 mm Hg, P = 0.039, Student t test) but not significantly so after Bonferroni adjustment. In multivariate regression analysis, decreasing age remained the only statistically significant independent predictor for the development of compartment syndrome (P = 0.006, regression coefficient = −0.0589) in diaphyseal tibial fractures. Conclusions: Tibial fractures of the diaphysis are more frequently associated with development of compartment syndrome than proximal or distal tibial fractures. More specifically, young patients with diaphyseal fractures are at risk for developing this complication and warrant increased vigilance and suspicion for compartment syndrome. A prospective study with sufficient power is needed to further identify risk factors associated with compartment syndrome in tibial fractures.

The Effects of Vitamin D Deficiency in Athletes

Vitamin D acts to maintain calcium and phosphate homeostasis within the body. It is now estimated that 1 billion people worldwide are vitamin D deficient. This problem is particularly important to athletes of all ages, as vitamin D plays a significant role in bone health, immune function, and physical performance. In the deficient state, the athlete may be at an increased risk for potential problems such as stress fractures, respiratory infections, and muscle injuries. The purpose of this article is to examine vitamin D deficiency and review its relationship to the athlete.

Effect of self-assembled peptide–mesenchymal stem cell complex on the progression of osteoarthritis in a rat model

Purpose To evaluate the efficacy of mesenchymal stem cells (MSCs) encapsulated in self-assembled peptide (SAP) hydrogels in a rat knee model for the prevention of osteoarthritis (OA) progression. Materials and methods Nanostructured KLD-12 SAPs were used as the injectable hydrogels. Thirty-three Sprague Dawley rats were used for the OA model. Ten rats were used for the evaluation of biotin-tagged SAP disappearance. Twenty-three rats were divided into four groups: MSC (n=6), SAP (n=6), SAP-MSC (n=6), and no treatment (n=5). MSCs, SAPs, and SAP-MSCs were injected into the knee joints 3 weeks postsurgery. Histologic examination, immunofluorescent staining, measurement of cytokine levels, and micro-computed tomography analysis were conducted 6 weeks after injections. Behavioral studies were done to establish baseline measurements before treatment, and repeated 3 and 6 weeks after treatment to measure the efficacy of SAP-MSCs. Results Concentration of biotinylated SAP at week 1 was not significantly different from those at week 3 and week 6 (P=0.565). Bone mineral density was significantly lower in SAP-MSC groups than controls (P=0.002). Significant differences in terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining between the control group and all other groups were observed. Caspase-8, tissue inhibitor of metalloproteinases 1, and matrix metalloproteinase 9 were diffusely stained in controls, whereas localized or minimal staining was observed in other groups. Modified Mankin scores were significantly lower in the SAP and SAP-MSC groups than in controls (P=0.001 and 0.013). Although not statistically significant, synovial inflammation scores were lower in the SAP (1.3±0.3) and SAP-MSC (1.3±0.2) groups than in controls (2.6±0.2). However, neither the cytokine level nor the behavioral score was significantly different between groups. Conclusion Injection of SAP-MSC hydrogels showed evidence of chondroprotection, as measured by the histologic grading and decreased expression of biochemical markers of inflammation and apoptosis. It also lowered subchondral bone mineral density, which can be increased by OA. This suggests that the SAP-MSC complex may have clinical potential to inhibit OA progression.

Bone Plug Versus Suture-Only Fixation of Meniscal Grafts Effect on Joint Contact Mechanics During Simulated Gait

Background: Meniscus allograft transplantation (MAT) is primarily undertaken to relieve the symptoms associated with meniscal deficiencies. However, its ability to restore normal knee joint contact mechanics under physiological loads is still unclear. Purpose: To quantify the dynamic contact mechanics associated with 2 commonly used fixation techniques in MAT of the medial compartment: transosseous suture fixation via bone plugs and suture-only fixation at the horns. Study Design: Controlled laboratory study. Methods: Physiological loads to mimic gait were applied across 7 human cadaveric knees on a simulator. A sensor placed on the medial tibial plateau recorded dynamic contact stresses under the following conditions: (1) intact meniscus, (2) MAT using transosseous suture fixation via bone plugs at the anterior and posterior horns, (3) MAT using suture-only fixation, and (4) total medial meniscectomy. A “remove-replace” procedure was performed to place the same autograft for both MAT conditions to minimize the variability in graft size, geometry, and material property and to isolate the effects of the fixation technique. Contact stress, contact area, and weighted center of contact stress (WCoCS) were quantified on the medial plateau throughout the stance phase. Results: Knee joint contact mechanics were sensitive to the meniscal condition primarily during the first half of the gait cycle. After meniscectomy, the mean peak contact stress increased from 4.2 ± 1.2 MPa to 6.2 ± 1.0 MPa (P = .04), and the mean contact area decreased from 546 ± 132 mm2 to 192 ± 122 mm2 (P = .01) compared with the intact meniscus during early stance (14% of the gait cycle). After MAT, the mean contact stress significantly decreased with bone plug fixation (5.0 ± 0.7 MPa) but not with suture-only fixation (5.9 ± 0.7 MPa). Both fixation techniques partially restored the contact area, but bone plug fixation restored it closer to the intact condition. The location of WCoCS in the central cartilage region (not covered by the meniscus) shifted peripherally throughout the stance phase. Bone plug fixation exhibited correction to this peripheral offset, but suture-only fixation did not. Conclusion: Under dynamic loading, transosseous fixation at the meniscal horns provides superior load distribution at the involved knee compartment after meniscal transplantation compared with suture-only fixation. Particular attention should be directed to the ability of medial MAT to function during the early stance phase. Clinical Relevance: Transosseous fixation via bone plugs provides superior load distribution of a transplanted meniscal allograft compared with suture fixation alone at time zero.

The Biomechanical Function of the Anterolateral Ligament of the Knee: Response

Dear Editor: We read with great interest the recently published study ‘‘The Biomechanical Function of the Anterolateral Ligament of the Knee’’ by Parsons et al. The authors tested 11 cadaveric knees and applied 2 loading conditions: (1) 134 N of anterior force and (2) 5 N m of internal torque at flexion angles between 0 and 90 . The in situ forces of the anterolateral ligament (ALL), anterior cruciate ligament (ACL), and lateral collateral ligament during these loading conditions were determined. The study is very important and deals with a highly up-to-date topic. We would like to give some thought-provoking points regarding the methods of the study, in particular regarding the principle of superposition, the surgical dissection, and the vector analysis of forces in the capsule. Subsequently, we would like to highlight the clinical importance of this paper and come up with future aims to improve patients’ outcome. To determine in situ forces of the proposed structure in this study, the principle of superposition was utilized. The principle of superposition requires 3 fundamental assumptions: (1) there is no interaction between the structures of interest, (2) the bony tissue is rigid relative to the ligaments, and (3) the position of each bone is accurately reproduced. To evaluate the in situ forces, it is important that the intact state of the knee is determined first. In this study, a medial parapatellar approach was performed to evaluate the integrity of the ACL prior to testing and to perform the cutting of the ACL. We would like to mention that an arthroscopic evaluation and cutting of the ACL via a small medial portal and maybe a central portal would ensure integrity of the anterolateral capsule as well and would cause less anatomic changes in the intact state. Furthermore, measurements of the anatomic dimensions of the proposed structure (ALL) and the course of dissection as reported by other groups should be included to provide readers better insight. To determine the in situ forces of structures during joint loading, it is important to distinguish the components of the capsule by separating them from each other to satisfy the principle of superposition. Subsequent cutting of the respective structures can be performed to evaluate their in situ forces. In this study, the separation was not accomplished, therefore the calculation of in situ forces cannot be accurate due to interaction between the components. Moreover, the authors reported in situ forces as percentage contributions. The percentage force contribution for each ligament was calculated by ‘‘dividing the magnitude of the force vector of the particular state of injury by the magnitude of the intact force vector.’’ However, this is not appropriate if there is the slightest probability that the directions of these vectors are not the same. Reporting results as a percentage of contribution can help to better understand their contribution to joint stability. Yet, the components of the in situ force vector representing each structure need to be calculated and have to be normalized to the magnitude of the externally applied load in the corresponding direction. This type of analysis must be completed for all 3 anatomic directions when a complex force such as an internal torque is applied. Subsequently, the quantity can be reported as a percentage to obtain the percentage contribution of the structure to the force-resisting joint motion. These issues likely undermine the study results and lead to incorrect assumptions about the in situ forces in the structures tested. What is the clinical importance of this study? This study is evaluating the biomechanical function of a proposed ALL using robotic technology. The results ultimately lead to the discussion of sufficient treatment options of injuries to the anterolateral capsule. In cases where an anatomic ACL reconstruction was performed and anterolateral laxity is still present, an extra-articular tenodesis might be beneficial. However, only a minority of patients will benefit. To identify those patients, quantification of rotary laxity is important. Increased pressure on the lateral compartment and restricted range of motion are pitfalls, which can lead to premature osteoarthritis and stiffness. This has to be considered and has to be discussed in detail. Future aims should be to quantify ACL-related injuries and to establish more individualized ACL surgery to maximize outcome and functional return of the patient. This study will blaze a trail for future biomechanical evaluation of the anterolateral capsule.

Porous tantalum patellar components in revision total knee arthroplasty minimum 5-year follow-up.

Revision total knee arthroplasty can be complicated by severe patellar bone loss, precluding the use of standard cemented patellar components. This study evaluated the midterm outcomes of porous tantalum (PT) patellar components. Twenty-three PT components were used in 6 men and 17 women (average age, 62 years). All patellae had less than 10-mm residual thickness. The PT shell was secured to host bone, and a 3-peg polyethylene component was cemented onto the shell. In 2 patients, the PT component was sutured directly to extensor mechanism. Average follow-up was 7.7 years (range, 5-10 years). At follow-up, the Knee Society scores for pain and function averaged 82.7 and 33.3, respectively, whereas the mean Oxford knee score was 32.6. Four patients underwent revision surgery. Survivorship was 19 (83%) of 23 patients. Porous tantalum patellar components can provide fixation where severe bone loss precludes the use of traditional implants. Failures were associated with avascular residual bone and fixation of components to the extensor mechanism.